The long-term goal of this proposal is to investigate the mechanism involved in human B and T cell activation. Previous studies in the murine model and preliminary studies employing human peripheral blood and splenic lymphocytes indicate that Fc fragments derived from papain digestion of IgG, aggregated immunoglobulin, and immune complexes are potent polyclonal B cell activators. The proposed studies have been designed to ascertain the cell-cell and cell-ligand interactions involved in polyclonal antibody production. The requirement for accessory cells and the nature of signals provided by these cells will be extensively investigated. This laboratory has recently shown that Fc fragments are capable of enhancing murine humoral and cellular immune responses, therefore, a comprehensive study of the potential adjuvant effects of Fc fragments on human immune responses will be conducted. The ability of Fc to potentiate both humoral and cell-mediated immune responses in the human will be studied. The potential use of Fc fragments as an immunotherapeutic agent in cancer management will be studied by assessing the ability of Fc to enhance natural killer cell activity.